Very long-chain polyunsaturated fatty acids (VLC-PUFA) of 20 or 22 carbon atoms are indispensable components of human nutrition. They are necessary for normal life-long physiology and benefit the well-being of the human body. Nutritionally important VLC-PUFAs include the ω3-fatty acids, eicosapentaenoic acid (EPA, 20:5ω3) and docosahexaenoic acid (DHA, 22:6ω3) and the ω6-fatty acid, arachidonic acid (ARA, 20:4ω6) and dihomo-y-linolenic acid (DGLA, 20:3ω6) which are the major components of membrane phospholipids of the retina, brain and testis. ARA and DHA are the predominant fatty acids in the human brain and breast milk. ARA is necessary for normal fetal growth, and cognitive development in infants. Many studies highly suggested supplementation of infant formula with DHA and ARA. Besides the structural function in membranes, ARA is the primary substrate in eicosanoids biosynthesis which regulates many physiological processes such as homeostasis, reproduction, immune and inflammatory responses.
Microalgae are the most efficient producers and one of the richest sources of VLC-PUFAs. Furthermore, algae can be used as sources of genes for the implementation of VLC-PUFA biosynthesis in genetically engineered oil crops. The genetic information on enzymes involved in the biosynthesis of VLC-PUFA in some algae led to in vivo applications of VLC-PUFA production in seed oil. The gene pool of the green freshwater microalga Parietochloris incisa (Trebouxiophyceae) is of special interest since it is the only known microalga able to accumulate extraordinary high amounts of ARA-rich triacylglycerols (TAG). When P. incisa is cultivated under nitrogen starvation, the condition triggering storage oil accumulation, ARA constitutes about 60 percent of total fatty acids (TFA) and over 95 percent of cellular ARA is deposited in TAG in cytoplasmic lipid bodies.
The biosynthesis of VLC-PUFA in microalgae follows two major pathways, designated as ω6 and ω3. In these pathways, linoleic acid (LA; 18:2ω6) and α-linolenic acid (ALA; 18:3ω3) go through sequential, Δ6 desaturation, Δ6 elongation and Δ5 desaturation, yielding ARA and EPA, respectively. E.g., in the red microalga Porphyridium cruentum and the green microalga P. incisa, oleic acid (18:1) is first desaturated to LA and .gamma.-linolenic acid (GLA, 18:3ω6) through Δ12 and Δ6 desaturations, followed by elongation to 20:3ω6 and Δ5 desaturation to yield ARA via the ω6 pathway. In P. incisa, the extraplastidial lipids, phosphatidylcholine (PC) and the betaine lipid, diacylglyceroltrimethylhomoserine (DGTS), are involved in the Δ12 and, subsequently, the Δ6 desaturations, whereas phosphatidylethanolamine (PE) along with PC are the suggested major substrates for the Δ5 desaturation of 20:3ω6 to 20:4ω6. The same enzymes are involved in the biosynthesis of VLC-PUFA through the ω3 pathway in the green microalga Ostreococcus tauri. 
VLC-PUFAs may also be generated by an alternative Δ8 desaturation pathway. E.g., in the marine haptophyte Isocrysis galbana and in the fresh water euglenophyte Euglena gracilis, where LA and ALA are first elongated by C18 Δ9-specific fatty acid elongase followed by sequential Δ8 and AS desaturations to ARA, DGLA or EPA. The extraplastidial Δ12 desaturase is an integral ER-bound protein which is responsible for the desaturation of oleic acid and production of LA, mainly on phosphatidylcholine (PC). Δ5 and Δ6 desaturases contain a fused cytochrome b5 domain in their N-terminus, serving as an electron donor, and introduce a double bond at a site closer to the carboxyl group than any of the pre-existing double bonds in the substrate fatty acid, thereby called ‘front-end’ desaturases. Desaturases with Δ6 or Δ5 activity have been isolated from various organisms, e.g., the nematode C. elegans, the fungus Mortierella alpina, the moss Physcomitrella patens, the liverwort Marchantia polymorpha and the algae Phaeodactylum tricornutum, Thalassiosira pseudonana and Ostreococcus tauri. Some of these desaturases have been introduced together with PUFA-specific elongases into constructs for transformation of yeast and oil seed plants to reconstitute VLC-PUFA biosynthesis in the heterologous organisms.